The overall goal of this proposal is to accelerate the translation of scientific results from observational and experimental studies into public health policy. Epidemiology is at a crossroads. The vast majority of studies of exposure-outcome relationships in observational and randomized settings alike ask questions about exposure effects: questions which relate to individuals, and to lifestyle choices. For example, a study might ask about how smoking cessation affects risk of heart attack in people with HIV - a question relating largely to exposure-disease etiology. Such estimates are useful, but they are only the first step in making effective public policy, which requires the articulation of a specifi health intervention, and issues of the uptake of the intervention and its real world effectiveness. At present, few methods exist for assessing interventional effects in complex longitudinal data with time-varying exposures: the mainstay of modern epidemiology. This proposal aims to develop and apply innovative epidemiologic methods to create policy-ready, actionable epidemiologic results. Specifically, we will develop and extend two of the g-methods: the parametric g-formula, and inverse probability weighted marginal structural models. We will apply these methodological innovations to critical and timely problems within HIV in both domestic and international contexts. First, we will examine smoking-associated morbidity and mortality among HIV-positive individuals in the United States from the national CNICS database, and estimate the impact of specific smoking cessation interventions on all-cause mortality in this population. Second, we will examine the joint effects of hormonal contraception and pregnancy on response to highly active antiretroviral therapy among HIV-positive women in South Africa, and estimate the impact of specific interventions to reduce unintended pregnancy in this population on population health outcomes including response to treatment. The proposed methods work will help to bridge the gaps between epidemiology and implementation science, and will thus have extremely broad application: not only to the critical issues in HIV, but to epidemiology and public health as a whole. The proposed substantive work will fill needed gaps in the HIV literature, and our approach - rooted in the methods we will develop - will be well-positioned to drive public health policy in these areas. Thus, we propose a high-risk, high-reward effort to create methods to move from exposures to interventions and from patients to policy: through clearly communicated and usable methodological innovation, and high-impact substantive applications.